March 8, 2005 | Researchers from the Broad Institute of Harvard and MIT have used DNA microarrays to reveal patterns of chemical modifications of chromatin, the complex of protein and DNA that makes up chromosomes. Writing in Cell, Broad researchers Bradley Bernstein, Stuart L. Schreiber, Eric Lander, and co-workers say they have produced "an unprecedented long-range view [of chromatin modification], three orders of magnitude greater in scale than prior studies, that reveals a series of insights into the structure and function of vertebrate chromatin."

Chromatin is composed of spools of DNA wrapped around proteins called histones. Chemical modifications of the histones lead to conformation changes that have profound effects on gene activity in health and disease.

The Broad researchers collaborated with Affymetrix to survey the chromatin modifications along chromosomes 21 and 22. They first isolated DNA regions in which one of the histones (H3) had been chemically tagged either with methyl or acetyl groups. Next, the Affymetrix microarrays were used to identify the DNA sequences associated with the tagged histones. The Broad Institute's Michael Kamal led the computational data analysis.

Not surprisingly, most of the mapped tags lie close to the known starting points of active genes. However, Bernstein's group also found tags sitting in regions near the same genes in both humans and mouse chromosomes, suggesting important functions. The researchers also surveyed the HOX genes, key developmental regulators, finding "huge stretches of genome, many thousands of base pairs in length, that are completely covered by tags," Bernstein says. These unique chromatin structures could be activating sets of HOX genes for specific developmental programs.

The chromatin data "will be an invaluable resource in our effort to define the regulatory network of the genome," Kamal says. Future studies of these tags may shed light on the molecular basis of cancers, including leukemia. "We're finding that there may be much less unimportant DNA in the genome than we thought," said Thomas Gingeras, Affymetrix vice president of biological sciences.